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体内中和树眼镜蛇毒素介导的黑曼巴蛇毒液的神经毒性的多克隆人免疫球蛋白抗体。

In vivo neutralization of dendrotoxin-mediated neurotoxicity of black mamba venom by oligoclonal human IgG antibodies.

机构信息

Department of Biotechnology and Biomedicine, Technical University of Denmark, Søltofts Plads 224, DK-2800, Kongens Lyngby, Denmark.

IONTAS Ltd., Iconix Park, London Road, Pampisford, Cambridgeshire, CB22 3EG, United Kingdom.

出版信息

Nat Commun. 2018 Oct 2;9(1):3928. doi: 10.1038/s41467-018-06086-4.

Abstract

The black mamba (Dendroaspis polylepis) is one of the most feared snake species of the African savanna. It has a potent, fast-acting neurotoxic venom comprised of dendrotoxins and α-neurotoxins associated with high fatality in untreated victims. Current antivenoms are both scarce on the African continent and present a number of drawbacks as they are derived from the plasma of hyper-immunized large mammals. Here, we describe the development of an experimental recombinant antivenom by a combined toxicovenomics and phage display approach. The recombinant antivenom is based on a cocktail of fully human immunoglobulin G (IgG) monoclonal antibodies capable of neutralizing dendrotoxin-mediated neurotoxicity of black mamba whole venom in a rodent model. Our results show the potential use of fully human monoclonal IgGs against animal toxins and the first use of oligoclonal human IgG mixtures against experimental snakebite envenoming.

摘要

黑曼巴蛇(Dendroaspis polylepis)是非洲大草原上最令人恐惧的蛇类之一。它的毒液具有很强的神经毒性,作用迅速,由树眼镜蛇毒素和α-神经毒素组成,如果未经治疗,中毒者的死亡率很高。目前,抗蛇毒血清在非洲大陆上非常稀缺,而且存在许多缺点,因为它们是从经过高度免疫的大型哺乳动物的血浆中提取的。在这里,我们通过结合毒液组学和噬菌体展示技术,描述了一种实验性重组抗蛇毒血清的开发。该重组抗蛇毒血清基于一组完全人免疫球蛋白 G(IgG)单克隆抗体,能够中和黑曼巴蛇全毒液介导的啮齿动物模型中的神经毒性。我们的结果表明,完全人源单克隆 IgG 对抗动物毒素具有潜在的用途,并且首次使用寡克隆人 IgG 混合物对抗实验性蛇咬伤中毒。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc71/6168529/1f873b3d8edb/41467_2018_6086_Fig1_HTML.jpg

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